Periodontal regeneration using ex vivo autologous stem cells engineered to express the BMP-2 gene: an alternative to alveolaplasty.

The regeneration of the periodontal attachment apparatus remains clinically challenging because of the involvement of three tissue types and the complexity of their relationship. Human recombinant bone morphogenic protein-2 (rhBMP-2) can accelerate the regeneration of bone and cementum and the insertion of periodontal ligament fibers but may lead to a deranged periodontal relationship, ankylosis and root resorption.This study evaluated a novel approach to regeneration of the periodontal attachment apparatus using a combination of ex vivo autologous bone marrow mesenchymal stem cells (MSCs) engineered by replication-defective adenovirus to express the BMP-2 gene and Pluronic F127 (PF127). Twenty-four periodontal defects were surgically created in 12 New Zealand white rabbits and randomly assigned to three experimental groups with MSCs: the advBMP-2 group; the advbetagal group; the MSC group and one control group: PF127 only. The regenerated periodontal attachment apparatus was assessed histologically and the total regenerated bone volume was calculated from three-dimensional computed tomography analysis.This approach regenerated not only cementum with Sharpey's fiber insertion, but also statistically significant quantities of bone, re-establishing a more normal relationship among the components of the regenerated periodontal attachment apparatus, which is beneficial for the maintenance of periodontal health.Ex vivo gene transfer using stem cells as vectors may provide an advantage of slower BMP-2 release, increasing cementogenesis. There is regeneration of the periodontal attachment apparatus, whereas direct usage of the protein (rhBMP-2) yields unhinged periodontal relationship. Thus, this approach may represent an alternative means for periodontal alveolar bone graft in clinical settings.

Innovative technique to reconstruct two branches of the right hepatic artery in living donor liver transplantation.

Hepatic arterial thrombosis is a critical complication in living donor liver transplantation (LDLT). Two separate branches of the right hepatic artery (RHA) are sometimes observed and addressed by anastomosis of the larger branch first, then checking backflow from the smaller branch. If not good, the smaller branch must be reconstructed. We used the cystic artery as a conduit for the reconstruction. Meticulous dissection was performed to identify all branches of the hepatic artery in the donor operation. The length of cystic artery preserved was as long as possible. The cystic arterial stump was anastomosed to the stump of the posterior branch the of RHA under microscopic guidance on the back table. Patency was checked through the stump of the anterior branch of the RHA. With this technique, only one orifice, the stump of right anterior hepatic artery, was used for hepatic artery reconstruction. We have performed this technique in two patients. Both had good arterial flow after living donor liver transplantation. This innovative technique is easy and safe, and requires only one anastomosis, which, in theory, decreases the adds of developing hepatic arterial thrombosis.

Ex vivo gene therapy in autologous bone marrow stromal stem cells for tissue-engineered maxillofacial bone regeneration.

This study examines the clinical relevance of tissue engineering integrating gene therapy and polymer science to bone regeneration. Bilateral maxillary defects (3 x 1.2 cm(2)) in 20 miniature swine were bridged with a bioresorbable internal splint. Constructs were created using ex vivo adenovirus bone morphogenetic protein (BMP)-2-mediated gene transfer to the expanded bone marrow mesenchymal stem cells (MSCs) 7 days before implantation. Controls were performed using adenovirus beta-galactosidase. The BMP-2 cell/construct displayed white solid bone formation after 3 months. Meanwhile, the hematoxylin and eosin and Von Kossa stains demonstrated exhibited mature woven bone with good mineralization. Additionally, three-dimensional computer tomography imaging revealed a nearly complete infraorbital rim repair. Quantitative analysis demonstrated a significant difference (P<0.001) in bone formation. Finally, biomechanical testing revealed no statistically significant difference in the maximal compressive strength of new bone formed by BMP-2 cell constructs and the normal maxilla. The data evidenced de novo bone formation capable of sustaining axial compressive loads. The measurement results showed that ex vivo replication defective adenovirus-mediated human BMP-2 gene transfer to MSCs enhances autologous bone formation in the repair of maxillary defects.